A combination of oral vitamin A (VitA) and intense aromatic chemosensory smell training (ST) by pulse aromatic stimulation will expedite the neurosensory recovery of olfaction in patients suffering from prolonged COVID-19-related olfactory dysfunction (OD).
This is an open-labeled randomised-controlled trial (RCT) investigating the safety and therapeutic efficacy of oral VitA in combination with ST for patients suffering from prolonged COVID-19-related OD. Prior to the initiation of treatment, all patients will receive subjective and objective olfactory assessments. Comprehensive ear, nose, and throat (ENT) examination will be performed to rule out alternative causes of OD. All participants will receive resting-state functional magnetic resonance imaging (rs-fMRI) of the brain before treatment as baseline evaluation. Patients with prolonged COVID-19-related OD will be assigned to the intervention (group A or B) or control (group C) arms: Intervention arm A. 14-day course of daily oral VitA 7500µg RAE (retinol activity equivalents) in combination with ST three times per day for 4 weeks; or B. ST three times per day for 4 weeks alone; or Control arm C. Observation In addition, healthy controls who were tested negative for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) will receive rs-fMRI brain scans for radiological comparisons. At the completion of the trial, subjective and objective olfactory assessments will be repeated to document clinical changes in olfaction. Follow-up rs-fMRI will be performed to document neuroradiological changes in the brain structures and cerebral network functional connectivity (FC).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
25
Metabolic supplement for neurogenesis at the olfactory apparatus
Handheld essential oil ultrasonication diffuser technology
Pamela Youde Nethersole Eastern Hospital
Hong Kong, Hong Kong
RECRUITINGThe University of Hong Kong, Queen Mary Hospital
Hong Kong, Hong Kong
RECRUITINGSubjective olfactory assessment
Subjective olfactory assessment by the Sino-Nasal Outcome Test (SNOT-22).
Time frame: 4 weeks
Objective olfactory assessment by the butanol threshold test (BTT)
Objective measurements of olfactory sensitivity, as determined by the detection of different concentrations of butanol.
Time frame: 4 weeks
Objective olfactory assessment by the smell identification test (SIT)
Objective categorization of olfactory status by the smell identification test (SIT).
Time frame: 4 weeks
Interim neuroradiological changes after 2 weeks of olfactory treatment
Group independent component (GIC) and cerebral network functional connectivity (FC) analyses of the olfactory, gustatory, somatosensory, and integrative networks using rs-fMRI scans, before and at 2 weeks after olfactory treatment in COVID-19 patients with olfactory dysfunction (OD)
Time frame: 2 weeks
Neuroradiological changes after olfactory treatment at the end of study
Group independent component analyses and functional connectivity analyses of the olfactory, gustatory, somatosensory, and integrative networks by resting-state functional MRI brain scans, before and after treatment in COVID-19 patients with olfactory dysfunction at 4 weeks.
Time frame: 4 weeks
Interim neuroradiological changes after oral vitamin A in combination with smell training versus smell training alone
Group independent component analyses and functional connectivity analyses of the olfactory, gustatory, somatosensory, and integrative networks by resting-state functional MRI brain scans, between combined VitA and smell training (ST) versus ST alone in COVID-19 patients with olfactory dysfunction at 2 weeks.
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Time frame: 2 weeks
Neuroradiological brain changes in the intervention group versus observation group at the end of study
Group independent component analyses and functional connectivity analyses of the olfactory, gustatory, somatosensory, and integrative networks by resting-state functional MRI brain scans, in the interventional versus control arms (observation) in COVID-19 patients with olfactory dysfunction at 4 weeks.
Time frame: 4 weeks
Neuroradiological brain changes in the intervention group versus healthy control group at the end of study
Group independent component analyses and functional connectivity analyses of the olfactory, gustatory, somatosensory, and integrative networks by resting-state functional MRI brain scans, in COVID-19 patients with olfactory dysfunction compared with healthy controls at 4 weeks.
Time frame: 4 weeks